THE  SYNTHESIS  AND  BROMINATION 
OF  BETA  BETA  DIPHENYL 
GLUTARIC  ACID 


BY 

WILLIAM  ROBERT  REICH 


THESIS 

FOR  THE 

DEGREE  OK  BACHELOR  OF  SCIENCE 

IN 

CHEMISTRY 


COLLEGE  OF  LIBEHAL  ARTS  AND  SCIENCES 

UNIVERSITY  OF  ILLINOIS 


1922 


. 


UNIVERSITY  OF  ILLINOIS 


p 

.192 


lay 


THIS  IS  TO  CERTIFY  THAT  THE  THESIS  PREPARED  UNDER  MY  SUPERVISION  BY 

^ 1 1 1 X '31™  f>Y\, 


ENTITLED JC’S.-P.xsnajLa 


3_p_  1 £ ri~_  RL  cTig  CA-Tj-L'i.z'i  _ 


IS  APPROVED  BY  ME  AS  FULFILLING  THIS  PART  OF  THE  REQUIREMENTS  FOR  THE 
DEGREE  OF  __JSach.sulo.r--- o£— Science. 

j_T3 Qh  e>  j g 3[*  y 


Instructor  in  Charge 


Approved  : 


^C.AKA 


f*  0 Y'SA.  T*_3^_ 


HEAD  OF  DEPARTMENT  OF 


The  author  wishes  to  acknowledge  the  helpful 
guidance  and  suggestions  given  by  Dr.  B.L.  Souther  in  the 
pursuit  of  these  investigations. 


Digitized  by  the  Internet  Archive 
in  2015 


https://archive.org/details/synthesisbrominaOOreic 


TABLE  OF  CONTENTS 


Page 


Theoretical  1 
Historical  4 
Experimental  9 
Summary  21 
Bibliography  22 


THEORETICAL 


The  object  of  this  work  was  the  preparation  of  a 
cyclopropene  in  order  to  study  its  reactions.  Very  few  substitut- 
ed cyclopropenes  have  been  prepared.  Feist1  prepared  methyl 

/C-COOH 


cyclopropene  dicarboxylic  acid,  CH^  - CH'^  and  Jones 

studied  some  of  its  reactions.  Perkin  and  Thorpe-'1  prepared  ethyl 
dibromo-  y3-  dimethyl  glutarate  in  the  expectation  that  the 
elimination  of  two  molecules  of  hydrogen  bromide  would  give  di- 
methyl cyclopropene  dicarboxylic  acid.  However,  they  did  not 
obtain  any  of  the  unsaturated  acid  and  concluded  that  it  was  so 
active  that  it  united  with  the  alcohol  present  as  soon  as  it  was 
formed  according  to  this  equation 


C-COOH 
(OH,) 2 o'll 

> - C-COOH 


+ C0Hc  OH  = (CH,)2  C( 

2 5 * ^ CH- 


^OCoHp 
c '"-COOH 


COOH 


Ingold  and  Thorpe4  have  performed  the  latest  invest- 
igations upon  cyclopropenes.  They  prepared  cyclopropene-dicar- 
boxylic  acid  but  from  its  reactions  it  could  not  be  ascertained 

whether  its  formula  was  this  ch^q_pqok  or  "tills  CH2vc  COOH 
It  was  supposed  that  the  two  forms  were  in  equilibrium  with 

each  other. 

If  -diphenyl-glutar ic  acid  is  brominated  and 
then  two  molecules  of  hydrobromic  acid  are  split  out  it  will  in 
all  probability  gi,re  a substituted  cyclopropene. 


/ 


.CHBr-COOH  . ... 

(C^Hc)p  c'  = 2H  Br  + (CgHc)2  c-sp 

o CHBr-COOH  0 p c“ 


.C-COOH 


C-COOH 


. 


I 


' 


' 


- 2 - 


From  this  equation  it  is  obvious  that  the  only  other  possibility 
would  be  for  a hydrogen  atom  to  split  from  the  phenyl  group  but 
this  would  be  contrary  to  the  ordinary  reactions  of  that  group. 
Accordingly  the  problem  resolves  itself  into  the  preparation  and 
bromination  of  y^.^-diphenyl  glutaric  acid. 

The  first  method  that  was  tried  was  by  the  action 
of  sodium  malonic  ester  on  benzophenone  chloride? 


(C6H5)2  C 012  + 2Na  [CHCCOOC^gj  = (C6H5)2  <qh ^000^ 


/-COOE 
p^n"COOH 
- tG6h5j2  ^COOH 


j 

COOC2H5 


/CHgCOOH 
= (C^r)  2 C^CH2C00H 


COOH 

Since  this  reaction  gave  a non-crystalline  resin- 
ous mass  which  was  a mixture  of  acids  it  was  given  up  in  favor  of 
other  methods. 

5 

Ethyl  y£,/?-diphenyl-/9- hydroxy  propionate  was  pre- 
pared by  the  following  reactions: 

Br 

BrCHg-COOEt  + Mg  = 

Br 


JlgBr 


Mg(  " + (C6Hc)2  c-0  = (c6hJ2  C 

CH2C00Et  ^ 3 

/0-MgBr 

(°6H5)2  C^CH2-C00Et  + H0H  = ^C6H5^2  CvCH2-C00Et  + Mg  OH  Br 


"CH2C00Et 

OH 


Bromine  was  substituted  for  the  hydroxyl  group  by 
means  of  phosphorus  tribromide  but  it  was  found  that  the  ethyl - 
p > p-  diphenyl- p - bromo-propionate  thus  formed  was  unstable 
since  it  gave  off  hydrobromic  acid  and  formed  ethyl- y^./^aiphenyl 
acrylate.  This  compound  was  therefore  too  unstable  to  work  with. 


. i u;  J&jlpi 


- 3 - 


Ethyl  diphenyl  acrylate  was  also  prepared  by 

the  dehydration  of  ^^-diphenylyS' hydroxy  propionic  acid  by 
means  of  acetic  anhydride  and  then  esterifying.  Malonic  ester 
reacted  very  smoothly  with  this  compound  in  the  presence  of 
sodium  ethylate  and  the  complete  absence  of  water,  according  to 
the  following  scheme. 

^CQOEt 

yCOOEt  v ^/°MNCOOEt 


(CgH5)2  C = CH-COOEt  + H2CsC00Et  - IC&h  C 


nCH2“  COOEt 


Upon  the  saponification  of  this  compound  and  sub- 
sequent heating  it  should  lose  carbon  dioxide  and  form  J3 , ^-di- 
phenyl glutaric  acid. 

'COOH  .CH^COOH 

= (c^)P  c; 

‘CH2-  COOH 

p>  ,J3  -diphenyl  glutaric  acid  can  probably  be 
brominated  directly  with  bromine  and  phosphorus  and  by  then  re- 
moving two  molecules  of  hydrobromic  acid,  the  desired  substituted 
cyclopropane  can  be  obtained* 


pu^COOH  .CHoC00H 

<*V8  = (^>2  C^cooh  + C°2 


- 4 - 


HISTORICAL 


In  order  to  obtain  an  idea  of  a method  of  prepara- 
tion and  the  properties  of  p, /3-diphenyl  glutaric  acid,  the  liter- 
ature was  searched  for  compounds  of  similar  structure,  namely, 

/3  -substituted  glutaric  acids.  The  methods  of  preparation  are 
given  below  and  the  properties  and  references  are  recorded  later 
in  tabular  form. 

1 

I.  Darbishire  and  Thorpe  prepared  p-  methyl 
glutaric  acid  by  the  action  of  ethyl  cyanacetate  on  the  ethyl 
ester  of  p>-  methyl  acrylate.  The  ethyl-  cx  -cyano- p -methyl  glu- 
tarate  formed  is  hydrolizea  by  means  of  dilute  sulfuric  acid. 

The  p>-  methyl  glutario  acid  is  recrystallized  from  concentrated 
hydrochloric  acid. 


II.  Blaise  and  Zault  prepared  Jl  substituted  glu- 
taric acids  by  converting  r substituted  c*  diketo  pimelic 

R ^QTI  PQQW 

acids  "to  corresP°nd-inS  dioximes,  reducing 

these  to  the  dinitriles  and  finally  hydrolizing  the  nitriles  to 
acids.  methyl,  y3-ethyl  and^^-hexyl  glutaric  acids  were  pre- 
pared in  the  same  way. 


III.  E.  Knovenagel  prepared  p -methyl  and  ]3  -iso- 
propyl— glutaric  acids  by  condensing  acetaldehyde  and  isobutyl 
aldehyde  respectively,  with  malonic  ester  in  the  presence  of  die- 
thylamine,  and  saponifying  the  resulting  product. 

IV.  j3  -acetoglutaric  acid  was  prepared  by  heating 
ethyl^yS?  -aceto-tricarballylate  in  the  presence  of  hydrogen 


1 References  are  given  in  table. 


* 

* 


. 


- 

■ 


- 5 - 


chloride.  Upon  heating  p -aceto  glutaric  acid  it  is  converted 
into  the  keto-dilactone  which  can  be  reduced  by  hydroiodic  acid 
in  the  presence  of  phosphorus  to  p -ethyl-glutaric  acid. 

V.  Micheal  obtained  p -phenyl  glutaric  acid  upon 
reacting  sodium  malonic  ester  with  ethyl  cinnamate  and  subsequent- 
ly saponifying  the  product. 

VI.  Avery  and  Bonton  prepared  benzal  malonic  ester 
by  reacting  benzaldehyde  and  malonic  ester.  This  benzalraalonic 
ester  was  then  reacted  with  sodium  malonic  ester  and  a good  yield 
of  /2>  -phenyl  glutaric  acid  was  obtained  upon  the  saponification 
and  heating  of  this  product. 

VII.  JS , p -dimethyl  glutaric  acid  was  prepared  by 
Perkin  by  saponifying  and  heating  the  product  obtained  from  the 
reaction  of  pp  -dimethyl  acrylic  ester  and  sodium  malonic  ester. 

VIII.  If  two  molecules  of  cyanacetic  ester  and  one 
molecule  of  acetone  are  allowed  to  react  for  one  month  in  the 
presence  of  a few  drops  of  diethylamine,  a ten  percent  yield  of 
dimethyl-methylene-dicyanacetic  ester  is  obtained.  This  ester 
can  be  hydrolyzed  to  p,f 3 -dimethyl  glutaric  acid  by  means  of  di- 
lute sulfuric  acid. 

IX.  Awers  obtained  a 35  percent  yield  of  p>  > [3  - 
dimethyl  glutaric  acid  by  the  reaction  of  potassium  malonic  ester 
on  p,  [2  -dimethyl  acrylic  ester. 

X.  Kommpa  prepared  Jfit J3  -dimethyl  glutaric  acid 

in  a unique  manner.  He  condensed  mesityl  oxide  with  sodium  malon- 
ic ester  and  upon  treating  the  product  of  this  reaction  with  hot 
barium  hydroxide  solution  he  obtained  dimethyl  hydroresorcin. 


. 


. 

* 

. 


« 


. 


- 6 - 


This  is  oxidized  almost  quantitatively  to  -dimethyl  glutaric 

by  sodium  hypobromite. 

XI.  Thole  and  Thorpe  prepared  ^3- substituted  glutar- 
ic acids  by  condensing  various  ketones  with  cyanacetaraide  and  sub- 
sequently hydrolyzing  by  means  of  sulfuric  acid.  The  ketones  used 
were  ethyl  methyl  ketone,  acetone  and  cyclohexanone. 

XII.  Meerwein  condensed  benzaldehyde  and  malonic  est- 
er in  the  presence  of  a small  amount  of  sodium  ethylate  and  upon 
saponification  he  obtained  phenyl  glutaric  acid.  p>-  o-nitro 
phenyl  glutaric  acid  was  made  in  the  same  way  using  o-nitro  ben- 
zaldehyde in  place  of  benzaldehyde.  It  was  also  made  by  nitrating 

-phenyl  glutaric  acid. 

Following  is  a table  of  the  properties  of  the  above 
mentioned  glutaric  acids.  The  method  of  preparation  is  designated 
by  the  Roman  numeral  directly  before  each  description.  The  follow- 
ing abbreviations  are  used: 


Et  OH 
Me  OH 
pet . 
sol. 


ethyl  alcohol 
methyl  alcohol 
petroleum  ether 
soluble 

slightly  soluble. 


si.  sol.  = 


- 


■ 


. . 


- 7 - 

Forrnula 

M.P. 

M.P.cf 

Anhy- 

dride 

Meth- 

od 

Solubility 

Ref  erenoe 

ch2-cooh 

CH^-9-H 
^ CH2-C00H 

S6° 

06  0 

S6° 

S7° 

46° 

41° 

47° 

I 

II 

III 

sol.  Et  OH 
Me  OH 
hot  H20 

si. sol. 

CH  Cl^ 
Ether" 
benzene 
pet . eth. 

J.Chem. Soo . S7 , 
1717 

Ann.  21  g,  150 
Bull.soc . chim.4 

1, 75 

Ber.  11,  25S5 

ch2cooh 

G2H5-C-H 

CHgCOOH 

73° 

73° 

B.P.15S0 
(13  ram.) 

II 

IV 

sol.  Et  OH 
Me  OH 

si.  sol. 

Ether 
benzene 
CH  Cl, 
pet-etnex 

Bull.soc .chim.4 
1,75 

Ann.  295,,  103 

„TT  CHp-COOH 

CH-7  1 

3CH-C-H 

ch3  CH2"C00H 

97° 

- 

III 

sol.  pet. eth 
Et  .OH 
C SP 
CH  Cl^ 

si . sol . 

benzene 

ether 

Ber.  11,  25S5 

CH  C%-COOH 

^CH-CHg-C-H 

ch3  6h2-cooh 

4S° 

- 

III 

sol.  ether 
Et  OH 
benzene 

si.  sol. 

pet . eth, 
C SP 
hot  H20^ 

Ber.  21,  25S5 

ch2cooh 

C^-C-E 

ch2cooh 

37° 

B.P.1940 
(12  mm. ) 

II 

sol.  ale. 
eth. 
benzene 

si.  sol. 

C.S2 

h2o 

Bull,  soc . chim 

^1, 75 

ch2cooh 

g^Hc-Q-h 

J ch2cooh 

137° 

140° 
142. 3C 

l6S° 

> 

V 

VI 

XII 

sol.  benzene 
Et  .OH 
pet . eth 

si.  sol. 
eth. 

hot  H20 
CH  Cl^ 

J.Prakt .C-hem.  2 

25,  352 

Am.  Cham.J.  20, 
511— 

Ann.  IbO,  345 

- s - 

Formula 

M.P. 

M.P. 

of  An- 
il yclrieb 

Meth- 
; oa 

Solubility 

Reference 

NO2  .CH2-C00H 
A-  C-H 
N ch2-gooh 

205° 

- 

XII 

sol.  pet.eth. 
benz ene 
e£  OH 
si.  sol. 
eth. 

CH  CI3 

Ann.  260,  3^5 

CHp-GOOH 

1 

CH3-  O—OH3 

ch2-cooh 

101° 

100° 

101° 

101° 

101° 

124° 

124° 

124° 

124° 

VII 

VIII 

IX 

X 

XI 

sol.  Et  OH 
Me  OH 
ether 
benzene 
pet . ether 

si.  sol. 
hot  HpO 
H Cl 

J .Chem.  Soc  .6£,  1457 
Ber.  H,  3530 
Ber.  28,  II30 
Ber.  22,  1421 
J. Chem. Soc . 23.,  429 

GHp-COOH 

1 c 

CgH^-C-CH^ 

D CH2“G00H 

S6° 

B.P. 

1S50 

XI 

sol.  Et  OH 
benzene 

si.  sol 
hot  H20 
H Cl 

J. Chem. Soc .99.429 

0 CHp-COOH 
« 1 

GH3-O-C-H 

ch2-cooh 

48° 

- 

IV 

sol.  Me  OH 
Et  OH 

si.  sol. 

ether 
benzene 
CH  Cl^ 

Ann.  295. 103 

CHp-OBg  CHd3  00H 
/ " \ / 

CH  C 

'CH2-C%  'CH2C00H 

. 

181° 

L 

73° 

XI 

sol.  Et  OH 
Me  OH 
benz ene 
ether 
si.  sol. 
hot  HpO 

c^s2 

J . Chem. Soc .99 , 429 

- 9 - 

EXPERIMENTAL 


Preparation  of  Benzophenone  Chloride  by  Friedel  and  Crafts 
Reaction. 

130  c.c.  of  carbon  tetrachloride  were  mixed  with  25 
gm.  anhydrous  aluminum  chloride  in  a 500  c.c.  flask  with  a reflux 
condenser  and  hydrochloric  acid  trap  attached.  100  gm.  of  dry 
benzene  was  then  added  slowly  by  means  of  a separatory  funnel  and 
the  mixture  was  allowed  to  react  for  four  hours.  The  mixture  was 
then  poured  into  cold  water  and  the  oily  layer  quickly  separated 
to  prevent  the  hydrolosis  of  the  benzophenone  chloride  to  benzo- 
phenone. The  excess  of  carbon  tetrachloride  was  removed  on  the 
steam  bath  and  the  remainder  of  the  solution  was  then  distilled 
under  50  m.m.  pressure,  the  fraction  from  204°-206°  being  collect- 
ed. The  yield  was  13  gm.  or  4 percent  of  the  theoretical  yield. 

6 

Preparation  of  Benzophenone  Chloride  from  Benzophenone. 

100  gm.  of  benzophenone  and  165  gm.  of  phosphorus 
pentachloride  were  heated  at  160°~1S0°G  for  four  hours  in  a flask 
with  a reflux  condenser  attached.  The  mixture  was  then  distilled 
under  50  m.m.  pressure,  the  fraction  200°-210°  being  collected. 
This  fraction  was  redistilled  under  the  same  pressure  and  the  pure 
benzophenone  chloride  was  collected  between  204°-206°c.  The  yield 
is  70  gm.  or  60  percent  of  the  theoretical.  The  benzophenone 
chloride  prepared  in  this  manner  is  a clear  liquid  with  a bluish 
fluorescence. 

7 

Reaction  of  Benzophenone  Chloride  and  Malonic  Ester. 

13.6  gm.  of  pure  malonic  ester  and  l.S  gm.  of  sodium 
were  allowed  to  react  to  form  sodium  malonic  ester  in  $0  c.c.  of 


> 


. 

. . 


- 


. 


* 

* 


* 


1 /.  ... 

■ 

• • 


- 10  - 


anhydrous  benzene.  10  gm.  of  benzophenone  chloride  were  then  adaed 
and  the  mixture  was  heated  on  the  steam  bath  for  15  hours.  The 
solution  was  then  washed  several  times  with  water  and  the  benzene 
was  evaporated.  A yellow  viscous  liquid  resulted.  This  liquid 
was  saponified  by  heating  at  100°  for  12  hours  with  13  gms . KOH  in 
40  c.c.  ethyl  alcohol.  This  alcoholic  solution  was  then  poured  in- 
to 300  c.c.  cold  water  and  the  water  was  extracted  with  ether  to 
remove  any  unchanged  ester.  The  clear  yellow  water  solution  was 
acidified  with  hydrochloric  acid  and  a cloudiness  resulted.  The 
acid  was  extraced  with  ether  and  the  ether  solution  was  washed 
with  25  percent  sodium  carbonate  solution  and  then  with  water. 

The  solution  was  dried  over  anhydrous  sodium  sulfate  and  the  ether 
was  evaporated  by  means  of  a current  of  dry  air.  A resinous  fluid 
was  obtained  which  would  not  crystallize  from  ethyl  alcohol,  ether 
or  benzene.  It  was  slightly  soluble  in  hot  water. 

In  order  to  analyze  this  acid  it  was  exactly  neutra- 
lized with  dilute  ammonium  hydroxide  and  the  silver  salt  was  then 
precipitated  by  adding  a slight  excess  of  silver  nitrate.  This 
precipitate  was  washed  with  alcohol  and  ether  and  dried  in  a 
vacuum  dessicator.  A weighed  amount  of  the  silver  salt  was  then 
placed  in  a crucible  and  ignited  to  pure  metallic  silver. 


Analysis 

I 

weight  of  silver  salt 

I 

.170S 

II 

.076S 

weight  of  silver 

.06g4 

.0311 

percent  of  silver 

40.0  fo 

40.4 $ 

Following  is  given  a table  of  the  salts  which  might  have  been 
formed  by  the  above  reactions: 


- 11 


w/C00Ag 

(CgHjr  ) 2 C(  ' C00AS 
b 5 " WCOOAg 
"COOAg 

Mol.  Wt. 

soo 

Percent  of 
s i lv  er 

54.0$ 

yCHLCOOAg 
(c6HR)  c d 

D 2 * CH2C00Ag 

49  g 

43.4  $ 

/COOAg 

(c6h5)  c = Cs 
0 3 d COOAg 

4S2 

44  .S$ 

4.  ^°6H5^2  C = CH-COOAg  331  32.4$ 

From  the  above  data  it  is  obvious  that  a mixture  of 
two  or  more  of  the  above  acids  were  obtained  by  the  reaction  be- 
tween benzophenone  chloride  and  malonic  ester. 

g 

Preparation  of  Mono-brom  Acetic  Acid. 

250  gm.  glacial  acetic  acid  and  13  gm.  of  sulfur  were 
mixed  in  a liter  flask  with  a reflux  condenser  and  bromine  trap 
attached.  66  J gm.  of  bromine  was  then  added  slowly  by  means  of 
a separatory  funnel.  The  mixture  was  allowed  to  react  on  a steam 
bath  until  the  bromine  disappears.  It  was  then  distilled  under 
30  mm.  presure,  produced  by  a water  pump,  and  the  fraction  between 
125°-135°  was  collected.  This  was  further  purified  by  distilling 
under  atmospheric  pressure,  the  pure  bromacetic  acid  coming  over 
at  207°-209°C.  The  yield  is  59  percent  of  the  theory. 

A 70  percent  yield  is  obtained  by  the  following  meth- 
od. 300  gm.  glacial  acetic  acid,  S50  gm*  bromine  and  20  c.c. 
acetic  anhydride  were  mixed  in  a liter  flask  with  a reflux  condens- 


- 12 


er  and  hydrobromic  acid  trap  attached.  This  mixture  ms  warmed  to 
50°  C and  then  allowed  to  react  slowly  for  several  days  or  until 
no  more  bromine  was  present.  It  was  then  distilled  in  the  same 
way  as  before.  This  method  has  the  advantage  over  the  other  meth- 
od because  no  troublesome  sulfur  by-products  are  formed  as  in  the 
first  method. 

Preparation  of  Ethyl-Brom-acetate. 

100  gm.  of  bromacetic  acid  and  Sp  c.c.  of  absolute 
ethyl  alcohol  were  mixed  and  saturated  with  hydrochloric  acid  gas. 
After  standing  over  night  the  mixture  was  again  saturated  and  al- 
lowed to  stand  for  six  hours.  It  was  then  poured  into  &00  c.c. 
ice  water,  and  the  ester  was  extracted  with  ether.  After  evaporat- 
ing the  ether  the  residue  was  distilled  and  the  following  fractions 
were  obtained. 


1500-  1550  c 

16 

gm. 

155°-  1600  c 

3^ 

gm. 

1600-  165°  0 

31 

gm* 

1650-  17 o°  c 

20 

gm. 

Since  the  ester  prepared  in  this  manner  had  no  de- 
finite boiling  point,  it  may  be  concluded  that  the  chlorine  from 
the  hydrogen  chloride  replaced  some  of  the  bromine  in  the  ester, 

thereby  giving  a mixture  of  chloracetic  and  bromacetic  ester. 

9 

Demole  has  found  that  an  equilibrium  mixture  of  monobrom  and  mono- 
chlor  acetic  acids  exists  when  hydrobromic  acid  is  added  to  mono- 
chlor  acetic  acid. 

Accordingly  the  following  method  was  used  to  obtain 
pure  ethyl  bromoacetate.  100  c.c.  ethyl  alcohol,  2^0  gm.  brom- 


- 


- 13  - 


acetic  acid  and  30  gm.  concentrated  sulfuric  acid  were  mixed  to- 
gether and  allowed  to  stand  for  six  hours.  The  mixture  was  then 
poured  into  £00  c.c.  of  cold  water  and  the  ester  layer  was  separat- 
ed. The  water  was  extracted  with  ether  to  remove  the  remainder  of 
the  ester.  After  evaporating  the  ether  the  residue  was  distilled, 
the  fraction  159°-  l60°  being  collected.  A ninety  percent  yield 
was  obtained. 

Preparation  of  E^hyl  y&/3  -diphenyl- -hydroxy  propionate. 

3 gm.  of  zinc  which  had  been  purified  by  boiling  with 
dilute  potassium  hydroxide  and  then  with  dilute  hydrochloric  acid 
and  finally  washed  with  alcohol  and  ether,  were  added  to  a solution 
of  IS. 2 gm.  of . benzophenone  and  20  c.c.  of  bromacetic  ester  in  90 
c.c.  of  dry  benzene.  The  mixture  was  refluxed  for  three  hours  but 
the  reaction  did  not  take  place  as  recorded  by  Rupe  and  Busolt.10 

The  same  amounts  of  benzophenone  and  bromacetic  ester 
were  then  dissolved  in  benzene,  which  was  dried  over  phosphorus 
pentoxide,  and  the  solution  was  refluxed  with  £ gm.  of  a zinc  cop- 
per couple  for  twenty  four  hours.  The  solution  was  then  poured 
into  cold  dilute  sulfuric  acid  and  after  mixing  thoroughly  the  re- 
action products  were  extracted  from  this  acid  solution  with  ether. 
The  thick  brown  liquid  which  was  left  upon  evaporating  the  ether 
was  dissolved  in  alcohol  and  after  standing  for  several  hours  a 
small  yield  of  ethyl-  -phenyl-  [3  - hy do rxy-hydrocinnamat  e crystall- 
ized out.  Upon  further  crystallization  benzophenone  wns  obtained* 
The  zinc  copper  couple11  which  was  used  was  made  by  covering  some 
pure  granulated  zinc  with  a two  percent  solution  of  copper  sulfate 
and  allowing  to  remain  until  the  solution  was  decolorized.  This 


* 

. 

* 


■ • 


• . 


. 


-14- 


was  repeated  and  the  couple  was  then  washed  with  alcohol  and  ether 
and  dried. 

Since  the  yield  was  so  small  by  the  above  method  the 
following  modification  was  tried  which  gave  very  good  results. 

10.4-  gm.  magnesium,  55*6  gm.  benzophencne  and  60  gm. 
of  ethyl  bromacetate  were  mixed  with  J>00  c.c.  of  absolute  ethyl 
ether  in  a 500  c.c.  flask  with  a long  reflux  condenser  attached. 
Upon  warming  to  about  25°  C a vigorous  reaction  soon  begam  which 
was  cooled  from  time  to  time  in  order  to  keep  it  under  control.  Af- 
ter the  reaction  had  subsided  the  mixture  was  allowed  to  remain  ov- 
er night  and  was  then  poured  into  cold  dilute  sulfuric  acid  to  hy- 
drolyze the  magnesium  compound  which  was  formed.  After  complete 
hydrolysis  the  -phenyl-  -hydroxy- hydro cinnamic  ester  was 

extracted  from  the  acid  solution  with  ether,  the  ether  was  evapora- 
ted and  the  ester  was  purified  by  crystallization  from  ethyl  alco- 
hol. It  separated  as  fine  white  needles  which  melted  sharply  at 
34°  C.  The  yield  was  S5  percent  of  the  theory. 

Bromination  of  ethyl -diphenyl- ^ -hydroxy-propionate. 

5 gm.  of  the  ester  were  dissolved  in  dry  benzene  and 
5 gm.  of  phosphorus  tribrornide  was  then  added  slowly.  The  mixture 
was  refluxed  gently  for  an  hour,  hydrobromic  acid  being  given  off. 
After  washing  the  benzene  solution  with  dilute  sodium  carbonate 
the  benzene  was  evaporated  and  a yellow  viscous  liquid  remained 
which  could  not  be  crystallized  from  alcohol  or  ether  and  which 
gave  no  Beilstein  test  for  halogen.  The  absence  of  bromine  was 
probably  due  to  the  splitting  out  of  hydrogen  bromide  to  form 
the  unsaturated  compound  ethyl- B.B  -diphenyl-acrylate. 


- 15  - 


The  same  reaction  was  repeated  using  anhydrous  ether 
as  a solvent  instead  of  benzene.  Aout  one  gram  of  a crystalline 
substance  melting  at  l6^°C  was  obtained  which  was  probably  di- 
phenyl acrylic  acid.  Also  an  amber  colored  liquid  was  obtained 
upon  evaporating  the  ether  which  gave  a positive  Beilstein  halogen 
test.  This  compound  which  was  probably  -diphenyl-  ft  - brom 
propionic  ester  gives  off  hydrogen  bromide  upon  gentle  warming. 

The  Action  of  Sodium  Malonic  ester  on  Ethyl -diphenyl' 

1 3 -brom-propionate. 

The  ester  made  by  the  preceding  reaction  was  dissolved 
in  30  c.c.  of  absolute  ether  and  to  this  was  added  some  sodium 
malonic  ester  solution  which  was  made  by  disolving  .33  gm.  of  sod- 
ium in  a solution  of  2.5  c.c.  of  malonic  ester  in  20  c.c.  of  ab- 
solute ether.  The  materials  were  allowed  to  remain  a room  tempera- 
ture for  several  days,  a white  precipitate  separating  out  in  the 
meantime.  It  was  then  poured  into  100  c.c.  of  cold  water  and  the 
ether  layer  was  separated.  The  water  was  extracted  with  ether  to 
remove  the  remainder  of  the  reaction  products.  Upon  evaporating 
the  ether  a light  brown  liquid  was  obtained  which  would  not  cry- 
stallize from  alcohol,  ether  or  benzene.  Since  thie  liquid  was 
an  ester  it  was  saponified  with  a slight  excess  of  alcoholic  po- 
tassium hydroxide  solution  without  heating.  After  reacting  for 
twenty  four  hours,  the  solution  was  acidified  with  hydrochloric 
acid  and  the  white  precipitate  was  filtered.  The  precipitate  was 
dissolved  in  hot  absolute  alcohol  and  upon  cooling  beautiful  white 
plates  separate,  which  have  a melting  point  of  lol°-  l62°c.  This 
acid  might  have  been  any  one  of  the  three  listed  below: 


- 


■ 


. 


■ 


- 16  - 


Formula 

Molecular 

Neutral 

Weight 

Equivalent 

(C6H5)2 

C = CH  COOH 

224 

224 

CHoCOOH 

(c6h5)2 

c £ 

CH2C00H 

284 

142 

COOH 

(c6h5)2 

c CH  COOH 

446 

148 

CH2  COOH 

Since  the  neutral  equivalents  of  the  above  acids  di- 
ffer considerably,  that  of  the  acid  obtained  was  determined* 

Results 

I.  .099^  gni.  of  acid  was  neutralized  by  4.6  c.c.  of  .1006  N. 
sodium  hydroxide  solution  giving  a neutral  equivalent  of  217 • 

II.  *1835  of  acid  was  neutralized  by  8*5  c.c.  of  .1006  N 
sodium  hydroxide  solution  giving  a neutral  equivalent  of  219 • 

These  results  identify  the  acid  as  being  y#/foiphenyl 
acrylic  acid  which  was  formed  merely  by  the  ethyl'/3,y0  -diphenyl- p - 
-brom-propionate  splitting  out  hydrobromic  acid  this  reaction  being 
hastened  by  the  presence  of  alkaline  sodium  malonic  ester* 

Preparation  of  p, p>  -dipheny 1-Acrylic  Acid. 

40  gm.  of  p>  - diphenyl-  JS>  -hydroxy  propionic  ester 
was  saponified  by  heating  with  one  and  one  half  times  the  theoreti- 
cal amount  of  25  percent  alcoholic  potassium  hydroxide  for  twenty 
four  hours.  It  was  then  diluted  with  water  and  acidified  with  hy- 
drochloric acid  after  removing  any  unchanged  ester  with  ether.  30 
gm.  of  acid  was  obtained  upon  filtering  the  acidified  solution. 

This  acid  is  dissolved  in  20. 3 gm*  of  acetic  anhydride 
and  heated  to  150°C  for  three  hours  in  the  presence  of  2 gm.  of 


- 17  - 

anhydrous  sodium  acetate.  It  is  then  poured  into  cold  water  where 
the  acid  was  precipitated  and  the  acetic  anhydride  was  decomposed* 
The  acid  was  filtered,  redissolved  in  dilute  sodium  carbonate  and 
this  solution  was  boiled  with  bone  black  to  remove  the  coloring 
matter.  Upon  removing  the  boneblack  and  reacidifying  this  solution 
the  acid  was  precipitated  as  a white  powder  which  melted  at  l60°- 
162°  C. 

Esterification  of  .p  -diphenyl-acrylic  acid. 

7 gm.  of  the  acid  were  dissolved  in  25  c.c.  of  abso- 
lute ethyl  alcohol  and  S c.c.  of  concentrated  sulfuric  acid  was  add- 
ed and  the  whole  refluxed  for  three  hours.  The  solution  was  poured 
in  200  c.c.  cold  water  and  the  ester  was  extracted  with  ether  and 
the  ether  was  washed  with  dilute  sodium  carbonate.  The  residue  left 
after  the  evaporation  of  the  ether  would  not  crystallize  from  alco- 
hol, benzene  or  petroleum  ether. 

Because  a crystalline  product  was  not  obtained  by  the 
preceding  method  this  method  was  tried.  7 gm-  of  the  acid  were 
dissolved  in  dilute  ammonia,  care  was  taken  to  use  no  excess  of 
ammonia.  An  excess  of  silver  nitrate  was  then  added  and  a white 
heavy  precipitate  was  formed.  This  precipitate  was  washed  with  al- 
cohol and  ether  and  then  dried.  It  was  placed  in  a flask  with  90 
c.c.  of  absolute  ether  and  14  c.c.  of  ethyl  iodide  was  then  added* 
Upon  refluxing  this  mixture  for  two  hours  a yellow  precipitate  of 
silver  iodide  separated.  This  precipitate  was  filtered  off  and  the 
ether  was  evaporated.  The  ester  was  then  recrystallized  from  abso- 
lute alcohol.  The  crystals  separated  as  white  plates  with  a melt- 
ing point  of  114°  C. 


. 


- 18  - 


Analysis  of  this  Ester. 


I 

II 

Weight  of  sample 

.1451  gm. 

.1901  gm. 

Weight  of  carbon  dioxide 

.4310  gm. 

.5617  gm. 

Percent  of  carbon 

gi.i  $ 

SO.  69  io 

Weight  of  water 

.0821  gm. 

.1094  gm. 

Percent  of  hydrogen 

6.34$ 

6.44  # 

Calculated  Composition 

Carbon 

so.  9$ 

Hydrogen 

6.4# 

Oxygen 

12-7* 

A Method  for  the  Preparation  of  Pure  Absolute  Alcohol. 

4-0  c.c.  of  alcohol  which  had  been  dried  over  lime  was 
poured  over  10  gm.  of  magnesium.  A small  piece  of  sodium  was  added 
to  start  the  reaction  between  the  alcohol  and  magnesium  to  form 
magnesium  ethylate.  4-50  c.c.  of  dry  alcohol  was  then  added  to  this 
magnesium  ethylate  solution  and  the  whole  was  refluxed  for  two  hours. 
It  was  then  distilled  without  coming  into  contact  with  the  air. 
Magnesium  ethylate  removes  the  last  traces  of  water  from  alcohol 
according  to  this  equation 

(c2h5°)0  Mg  + 2H0H  = 2C2H50H  + Mg(0H)2 

Action  of  Malonic  Ester  on  Ethyl-  -diphenyl-acrylate. 

6 gm.  of  ethyl- p, y3  -diphenyl  acrylate  and  4.5  gm.  of 
malonic  ester  were  dissolved  in  70  c.c.  of  absolute  alcohol  which 
was  prepared  by  the  preceding  method.  .4  gm.  of  sodium  dissolved  in 
8 c.c.  of  absolute  alcohol  was  then  added  and  the  mixture  was  re- 


* 


* 


- 


* 


. • 


. . 


- 19  - 

fluxed  on  the  steam  bath  for  twenty  four  hours  and  then  allowed  to 
remain  at  room  temperature  for  seven  days.  At  the  end  of  thi3  time 
it  was  poured  into  200  c.c.  of  very  dilute  hydrochloric  acid  and  a 
white  solid  separated.  This  filtered  off  and  the  remainder  of  the 
ester  was  removed  from  the  acid  solution  by  extracting  with  ether. 
The  white  precipitate  was  then  dissolved  in  ether  and  washed  first 
witha  dilute  sodium  carbonate  solution  and  then  with  water  several 
times.  The  ether  was  then  evaporated  and  the  ester  was  crystalliz- 
ed from  ethyl  alcohol.  4-  gm.  of  white  leaf  like  crystals  were  ob- 
tained which  melted  at  15&°  C,  The  compound  which  was  obtained  is 
probably  represented  by  this  formula 


(c6k5)2 


pTjxCOOCpHc 

vn'C00C2Hg 

ch2cooc2h5 


Analysis  of  this  Compound 


I 

II 

Weight  of  sample 

♦3*317 

.1376 

Weight  of  carbon  dioxide 

.973^ 

.3511 

Equivalent  of  carbon 

.2656 

.9577 

Percent  of  carbon 

69.6/0 

69.6/0 

Weight  of  water 

.2211 

.0632 

Equivalent  of  hydrogen 

.02476 

.OO9S36 

Percent  of  hydrogen 

6.7$ 

6.5/* 

Calculated  Results 


Carbon 

Hydrogen 

Oxygen 


69  .9  /o 
6.2% 
23  • yfo 


20  - 


Dehydration  of  Ethyl  -diphenyl-  -hydroxy-propionate. 

5 gm.  of  -diphenyl-  p -hydroxy-propionic  ester 

were  heated  with  S c.c.  of  acetic  anhydride  on  an  oil  bath  at  150° 
C.  for  four  hours.  At  the  end  of  this  time  it  was  poured  into  cold 
water,  which  decomposed  the  acetic  anhydride.  The  white  precipit- 
ate is  filtered  off  and  crystallized  from  hot  absolute  alcohol. 

It  is  found  to  be  identical  with  the  ester  made  by  the  preceding 
method. 


♦ 

. 

* 


. 


21  - 


SUMARY 

c h lor  idfc. 

1.  It  was  found  that  benzophenone/\does  not  react  smooth 
ly  with  sodium  malcnic  ester. 

2.  A new  method  was  devised  for  the  preparation  of  mono 
brom-acetic  acid  using  acetic  anhydride  as  a catalyst.  This  meth- 
od gave  a clean  reaction  and  a good  yield. 

3»  Ethyl  mono-bromo-acetate  was  made  in  good  yield  from 
this  acid  using  sulfuric  acid  as  a catalyst.  Hydrogen  chloride 
gives  a mixture  of  esters. 

4-.  Ethyl-  prfS  -diphenyl-/^  - hydroxy-propionate  could 
not  be  prepared  by  means  of  the  Reformatsky  reaction  from  mono- 
brom-acetic  ester  and  benzophenone  as  given  in  the  literature. 
However,  when  magnesium  was  substituted  for  zinc  the  reaction  went 
smoothly. 

5.  Ethyl-  -diphenyl  - -bromo-propionate  was 

found  to  be  unstable,  breaking  down  into  ethyl-y?<^ -diphenyl  acry- 
late and  hydrogen  bromide. 

6.  Malonic  ester  reacted  with  ethyl-  fb , -diphenyl 

acrylate  in  fair  yield  to  form  the  tri-ethyl  ester  of  ( -di- 

l 

phenyl-  - carboxy)  ethyl  malonic  acid. 


- 


. 


- . ■ 


* 


* 


22 


BIBLIOGRAPHY 
1.  Ber.  26,  750  (1&93) 


2. 

J.  Chem.  Soc.  S7 . 

1062 

(1905) 

3* 

J.  Chem.  Soc.  79 , 

732 

(1901) 

4. 

J.  Chem.  Soc.  119 > 

2001 

(1921) 

5.  Ber.  40,  453^  (190?) 

6.  Ber.  2,  90S  (IS72) 

7.  Ber.  12,  1433  (1*99) 

S.  Bull.  Soc.  Chim  3 I,  365  (IS92 

9.  Ber.  2,  56I  (IS76) 

10.  Ber.  40,  453S  (1907) 

11.  Organic  Chemistry,  Perkin  and  Kipping,  page  56  (1917) 

N.B.  The  references  for  the  compounds  mentioned  in  the 
historical  section  are  given  in  the  table  at  the  end  of  that  di- 
vision. 


